The goal of this Phase I SBIR proposal is to test the feasibility of an intra-tissue antimicrobial surgical wound matrix in the prevention of superficial surgical site skin infections. Surgical Site Infections (SSI) are the second most common type of health care?associated infection (HAI), occurring in 2% to 5% of patients undergoing surgery in the United States, and accounting for approximately 2.0% of deaths due to health care- associated infections. These infections have resulted in 3.7 million excess hospital days, and close to $10 billion in health care expenditure annually. Current methods for SSI prevention include preoperative and perioperative systemic antibiotic use, perioperative application of antibiotic drug-containing (gentamicin, vancomycin) dressings or beads, and strict adherence to OR sterile technique procedures. The efficacy of systemic antibiotic use is significantly reduced by the requirement to adhere to carefully timed drug delivery due to short half-lives of less than 2 hours. The use of topical antibiotics has been challenged by the limited efficacy. Both systemic and topical antibiotic uses are plagued by inefficacy against multi-drug resistant organisms (MDROs). G4Surg, the proposed product overcomes current limitations by preventing/eliminating infection through a unique mechanism of action that is broad spectrum antibacterial. G4Surg takes advantage of charge composition to exert toxicity against Gram- positive and -negative bacteria (including antibiotic resistant strains). Furthermore, G4Serg relies only on sequences for antimicrobial charge ratio, and therefore is cell friendly, non-inflammatory, and nontoxic. To establish feasibility for the treatment of diabetic wounds, we propose the following two specific aims: Specific Aim 1: Through in vivo safety studies, demonstrate biocompatibility of G4Surg during incisional wound healing. Specific Aim 2: Through in vivo efficacy studies, demonstrate G4Surg's ability to clear bacteria infected abdominal incisional wounds. In SBIR Phase II, we will validate G4Surg efficacy in infected wound healing in a large animal model, test a wider range of bacterial strains in planktonic and biofilm forms, and execute GLP studies for our FDA submission.